期刊
THERANOSTICS
卷 11, 期 19, 页码 9376-9396出版社
IVYSPRING INT PUBL
DOI: 10.7150/thno.64706
关键词
Metformin; cardiovascular diabetology; endothelial function; diabetes; panvascular disease
资金
- National Natural Science Foundation of China [81941022, 81530025, 82070464]
- Strategic Priority Research Program of Chinese Academy of Sciences [XDB38010100]
- Program for Innovative Research Team of The First Affiliated Hospital of USTC [CXGG02]
- Anhui Provincial Key Research and Development Program [202104j07020051]
- Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program [2017BT01S131]
- Hefei Comprehensive National Science Center [BJ9100000005]
- Hefei Municipal Development and Reform Commission Emergency Funding for COVID-19 disease
Metformin, as a first-line treatment for diabetes, improves endothelial dysfunction through various pathways and has a positive impact on cardiovascular complications.
As a first-line treatment for diabetes, the insulin-sensitizing biguanide, metformin, regulates glucose levels and positively affects cardiovascular function in patients with diabetes and cardiovascular complications. Endothelial dysfunction (ED) represents the primary pathological change of multiple vascular diseases, because it causes decreased arterial plasticity, increased vascular resistance, reduced tissue perfusion and atherosclerosis. Caused by biochemical injury, ED is also an independent predictor of cardiovascular events. Accumulating evidence shows that metformin improves ED through liver kinase B1 (LKB1)/5'-adenosine monophosphat-activated protein kinase (AMPK) and AMPK-independent targets, including nuclear factor-kappa B (NF-kappa B), phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt), endothelial nitric oxide synthase (eNOS), sirtuin 1 (SIRT1), forkhead box O1 (FOXO1), kruppel-like factor 4 (KLF4) and kruppel-like factor 2 (KLF2). Evaluating the effects of metformin on endothelial cell functions would facilitate our understanding of the therapeutic potential of metformin in cardiovascular diabetology (including diabetes and its cardiovascular complications). This article reviews the physiological and pathological functions of endothelial cells and the intact endothelium, reviews the latest research of metformin in the treatment of diabetes and related cardiovascular complications, and focuses on the mechanism of action of metformin in regulating endothelial cell functions.
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